Journal
REPRODUCTION
Volume 146, Issue 6, Pages 637-645Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/REP-13-0146
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Funding
- National Key Scientific Program of China [2011CB944303]
- National Natural Science Foundation of China [81070529, 31271244, 31100841, 81270740]
- Promotion Program for Shenzhen Key Laboratory [CXB201104220045A]
- Shenzhen Projects of Science and Technology [200901015, 201202035]
- Biobank of Complex Diseases in Shenzhen [CXC201005260001A]
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Sperm quality declines with aging; however, the underlying molecular mechanism remains elusive. The cystic fibrosis transmembrane conductance regulator (CFTR) has been shown to play an essential role in fertilizing capacity of sperm and male fertility. This study aimed to investigate the involvement of age-dependent CFTR downregulation in lowering sperm quality in old age. Two hundred and one healthy fertile men of three age groups (20-40 years, n=64; 40-60 years, n=61; and >60 years, n=76) were recruited. Expression of CFTR was determined by RT-PCR, western blot, and immunofluorescence staining. Collected sperm were treated with CFTR inhibitor or potentiator. Sperm quality was assessed by motility and bicarbonate-induced capacitation. The results showed that the expression of CFTR on the equatorial segment and neck region of sperm was significantly decreased in an age-dependent manner. Reduction of CFTR expression in sperm from old men was correlated with lowered forward motility and decreased HCO3- sensitivity required for sperm capacitation. Activation of CFTR by genistein partially rescued the decreased forward motility in sperm from old men. Decreased CFTR expression in sperm was also found to be associated with lowered sperm quality in aging mice. These results suggest that age-dependent downregulation of CFTR in sperm leads to lowered sperm quality in old age sperm. CFTR may be a pontential target for rescuing sperm motility as well as a fertility indicator in old age men.
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